Cross-Linking Porcine Pericardium by 3,4-Dihydroxybenzaldehyde: A Novel Method to Improve the Biocompatibility of Bioprosthetic Valve

Abstract

Heart valve replacement is an effective therapy for patients with moderate to severe valvular stenosis or regurgitation. Most bioprosthetic heart valves applied clinically are based on cross-linking with glutaraldehyde (GLUT), but they have some drawbacks like high cytotoxicity, severe calcification, and poor hemocompatibility. In this study, we focused on enhancing the properties of bioprosthetic heart valves by cross-linking with 3,4-dihydroxybenzaldehyde (DHBA). The experiment results revealed that compared with GLUT cross-linked porcine pericardium (PP), the relative amount of platelets absorbed on the surface of DHBA cross-linked PP decreased from 0.294 ± 0.034 to 0.176 ± 0.028, and the activated partial thromboplastin time (APTT) increased from 9.9 ± 0.1 to 15.2 ± 0.1 s, indicating improved hemocompatibility. Moreover, anticalcification performance and cytocompatibility were greatly enhanced by DHBA cross-linking. In conclusion, the properties of bioprosthetic valves could be effectively improved by processing valves with a DHBA-based cross-linking method.

Hyaluronic Acid-Grafted Bioprosthetic Heart Valves Achieved by Copolymerization Exhibited Improved Anticalcification and Antithrombogenicity

“…The higher tangent modulus and more stable structure were attributed to a higher crosslinking degree. 33,45 GA-HA had a denser fiber structure than GA (Figure 3A). HA grafting increased the crosslinking degree and covered the surface of the pericardium, which could protect collagen fibers from degradation by collagenase and increase the stability of GA-HA.…”

Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization

“…The remaining amino groups were detected by the ninhydrin assay according to a previous study [ 29 ]. Briefly, the heart valve samples of each group were cut into 5 ​mm ​× ​5 ​mm pieces and then placed into a small centrifuge tube, followed by the addition of 1 ​mL of ninhydrin solution (ethylene glycol solution with 4% ninhydrin was mixed with an equal volume of 0.2 ​M citrate acid solution containing 0.16% Tin chloride, pH ​= ​5).…”

“…Animal experiments were approved by the Ethical Committee of Sichuan University. The ex vivo antithrombogenicity assays were performed according to previous reports [ 29 ]. Samples of each treatment group (n ​= ​6) were cut into 0.5 cm ​× ​1 ​cm strips and immersed in 75% ethanol overnight, followed by rinsing with normal saline three times.…”

The path to a hemocompatible cardiovascular implant: Advances and challenges of current endothelialization strategies

“…Therefore, from a translational perspective, less cytotoxic strategies that promote long-term EC proliferation are needed. The use of non-glutaraldehyde reagents, the application of biodegradable hydrogels, crosslinking with drug-loaded nanoparticle, the use of RGD peptides, and decellularization techniques are all tissue engineering strategies that have been developed to modify the surface of heart valves (95)(96)(97)(98)(99)(100)(101). Biomimetic acellular ECM-based TEHVs are manufactured from a polymer composite (PGA/P4HB) and an in vitro grown ECM, which are subsequently decellularized leaving a cell-free construct.…”